International Union of Pure and Applied Chemistry Chemistry and the Environment Division* Significance of Impurities in the Safety Evaluation of Crop Protection Products

There may be substantial differences in the chemical composition of technical-grade products of the same active ingredient manufactured under different conditions, from different raw materials, or by different routes of synthesis. Resulting differences in impurity content may significantly affect the toxicological properties of pesticide products. Relevant impurities are those that may exhibit pronounced toxic effects compared to the active ingredient, affect phytotoxicity or physical properties of formulations, result in undesirable residues in food, or cause environmental contamination. The first safety assessment of an active ingredient by a regulatory body considers toxicological data developed on a representative batch of technical products, with the assumption that the material produced commercially by the original or generic manufacturers has an equal or higher content of active ingredient and contains the same or fewer impurities at equal or lower concentrations as the fully characterized technical product used in the toxicological tests. Three steps are essential for ensuring the safety of commercial technicalgrade pesticide products, whether produced by the original manufacturer or by generic manufacturers. First, the identity and chemical structure of the impurities must be elucidated. This should include positive identification of major (≥1 %) and all toxicologically or environmentally relevant impurities, and characterization of minor impurities (>0.1 %). Second, in addition to recognition of a minimum active ingredient content, official specifications should also list relevant impurities and their maximum permissible concentrations. Implementation of these specifications should be aided by a decision-making scheme for establishing similarity of subsequently evaluated technical products. Third, appropriate analytical methods for the detection and quantification of impurity levels should be developed and employed in a quality-monitoring program associated with the manufacturing and formulation process. RECOMMENDATIONS OF THE IUPAC COMMISSION ON AGROCHEMICALS AND THE ENVIRONMENT 1. Detailed information on the composition of the technical active ingredient of the pesticide to be registered and toxicological studies applicable to the particular product should always be made available to regulatory agencies. 2. Relevant impurities should be defined as those that are more toxic than the pure active ingredient or raise other toxicological concerns, cause phytotoxicity, taint food commodities, affect the physical properties of formulations, or result in significant residues in food or the environment. 3. The relevant impurities should be named and their maximum permissible concentration should be specified in the registration documents as well as in Food and Agriculture Organization (FAO) Specifications of Plant Protection Products. Other impurities may be considered confidential. 4. The toxicological evaluations of the FAO/WHO (World Health Organization) Joint Meeting on Pesticide Residues, based on a specified technical-grade material, are carried out to assess the safety of food containing pesticide residues. These evaluations are not designed to cover aspects A. AMBRUS et al. © 2003 IUPAC, Pure and Applied Chemistry 75, 937–973 938